Previous work from this laboratory performed on bone marrow and blood cells has provided new information on the orderly step-wise assembly of cellular organelles during differentiation and their reorganization and participation in the function of these highly specialized cells. The major techniques applied are light microscopy on intact biopsy specimens and electron microscopy of enzyme and immunocytochemical preparations in addition to tissue culture. More specifically, the present objectives of this renewal application are as follows: 1) to continue to study the lysosomal pathway of certain blood cells, particularly phagocytes, with emphasis on the formation of endosomes and emchanisms of acidification. In particular, we shall try to identify the organelles where pH regulation may occur; 2) to investigate the secretory pathway, Golgi traffic, and exocytosis pathway of certain functional secretory products of macrophages at different stages of maturation and activation. We are basically asking the question--When in the life span are certain products synthesized, and what organelles are involved in their synthesis and utimate utilization?; 3) to carry out in vitro and in vivo studies of bone marrow stromal cells, particularly fibroblasts, which may be responsible for the support of, or the transfer of, hematopoietic environment. In brief, we are trying to better define the function of the "reticulum cells" of bone marrow stroma; 4) to continue to adapt and improve immunocytochemical techniques for the study of bone marrow cells. Compositely, this work will lead to a better understanding of the differentiation, functions, and interrelationships of bone marrow cells, particularly those responsible for the inflammatory response to infection or injury (i.e., host defense).